Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors

NCT06414460 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ISM3412-101
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 9

Brief Summary

The study has consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2). The primary objectives of this study are to evaluate the safety and tolerability of ISM3412 in participants with locally advanced/metastatic solid tumors, and to determine the RP2D of ISM3412.

Conditions

Locally Advanced/Metastatic Solid Tumors

Keywords

Methionine adenosyltransferase 2A (MAT2A); homozygous MTAP deletion; MAT2A inhibitor; ISM3412

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicity (DLT) events

  To evaluate the safety and tolerability of ISM3412.

  31 days

• Incidence and severity of adverse events (AEs)

  To evaluate the safety and tolerability of ISM3412.

  Approximately 30 months

• Recommended phase 2 dose (RP2D)

  To determine the RP2D of ISM3412.

  Approximately 30 months

Secondary Outcomes (7)

• Maximum observed concentration (Cmax)

  Approximately 30 months

• Time of maximum observed concentration (Tmax)

  Approximately 30 months

• Area under the concentration-time curve (AUC)

  Approximately 30 months

• Terminal half-life (t1/2)

  Approximately 30 months

• Objective response rate (ORR)

  Approximately 30 months

Study Arms (2)

Part 1 Dose Escalation

EXPERIMENTAL

Patients will receive ISM3412 once daily in sequential cohorts of increasing doses.

Drug: ISM3412

Part 2 Dose Selection Optimization

EXPERIMENTAL

Participants will be randomized to receive one of the two selected dose levels of ISM3412 once daily determined by Study Review Committee.

Drug: ISM3412

Interventions

ISM3412 DRUG

ISM3412 will be administered orally once daily.

Part 1 Dose Escalation; Part 2 Dose Selection Optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants with age ≥18 years at the time of signing the informed consent.
• Histologically confirmed unresectable locally advanced or metastatic solid tumors with confirmed homozygous MTAP deletion, who have disease progression after standard therapy, intolerable to standard therapy, or for whom no standard therapy exists.
• Have measurable or evaluable lesions in Part 1 and at least one measurable target lesion in Part 2 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Participants must provide a documentary evidence of homozygous MTAP deletion; or provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or at least 15 FFPE tumor tissue slides, or perform tumor tissue biopsies for a confirmatory genetic test indicating homozygous MTAP deletion.
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
• Life expectancy of ≥12 weeks as judged by the investigator.
• Adequate organ function as determined by medical assessment.
• Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.

You may not qualify if:

• Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
• Participation in other therapeutic clinical studies within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
• Anti-tumor therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogues, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter prior to first dose of study treatment.
• Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
• History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
• Previous history of, or presence of Gilbert's syndrome.
• Previous history of myelodysplastic syndrome.
• Prior solid organ or hematopoietic stem cell transplant.
• Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
• Have serious cardiovascular or cerebrovascular disease as per protocol.
• Presence of uncontrolled systemic infection as per protocol.
• Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition.

Sponsors & Collaborators

• InSilico Medicine Hong Kong Limited: lead

Study Sites (9)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Smilow Cancer Hospital at Yale New Haven Breast Center

New Haven, Connecticut, 06520-8028, United States

RECRUITING

Community Cancer Center North

Indianapolis, Indiana, 46250-2042, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4095, United States

RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

RECRUITING

Sun Yat-sen university cancer center

Guangzhou, Guangdong, 510030, China

RECRUITING

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

RECRUITING

Shanghai Gobroad Cancer Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Central Study Contacts

Rebecca Griffith

CONTACT

+86 021-50831718; Insilico-Clinicaltrial@insilico.ai

Rebecca Griffith

CONTACT

+1 (254) 265-2782

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 16, 2024
• Study Start: April 25, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: December 11, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4); US (5)